Researchers from Osaka University discovered that a previously undiscovered mutation might induce dilated cardiomyopathy, which is one of the leading causes of heart failure, in a study published in the journal ‘Science Translational Medicine.’
The human heart, the size of a fist and placed directly behind and slightly to the left of the breastbone, beats 100,000 times every day on average. Conditions that prevent the heart from pumping blood properly, on the other hand, might create major issues and necessitate a heart transplant.
Cardiac arrest is an incurable illness in which the heart is no longer able to satisfy the body’s blood supply demands. It is one of the leading causes of mortality, affecting about 40 million people globally and posing a major public health issue. A condition known as dilated cardiomyopathy is one of the primary causes of heart failure (or DCM). DCM is characterized by heart chamber dilatation and pumping dysfunction. DCM is typically hereditary and has a genetic foundation, according to previous study. However, in up to 80% of familial DCM cases, the genetic mutation responsible for the illness is still unknown.
A gene termed BAG5 was discovered to be a new DCM causal gene by the study team. First, they looked at patients from various families, finding a link between BAG5 gene loss of function mutations and DCM. The researchers discovered that this mutation is completely penetrant, indicating that 100% of those who carry it will acquire the illness. They discovered that mice lacking BAG5 had the same symptoms as humans with DCM, including dilation of the heart chambers and abnormal heart rhythm, in a mouse model of dilated cardiomyopathy. This suggested that mutations that disable BAG5’s function can result in cardiomyopathy.
“”We also showed that delivery of an AAV9-BAG5 vector in a mouse model may restore cardiac function after establishing that BAG5 mutations lead to loss of functional BAG5 protein,” said Dr. Yoshihiro Asano, senior author of the research. This discovery shows that gene therapy with adeno-associated viruses (AAV) should be examined further as a therapeutic option for individuals with BAG5 deficiency who do not need a heart transplant.” AAV gene therapy is a novel type of treatment targeted at correcting faulty genes in disorders with a hereditary aetiologic, such as DCM. As a result, our discoveries have cleared the path for a future gene therapy-based precision medicine treatment.
